Continuous bioprocessing for recombinant protein production in Bacillus subtilis : opportunities and challenges

Ivanovski, Andrej (author), Bratkovič, Tomaž (author)

The Gram-positive bacterium Bacillus subtilis has long been used for industrial protein production owing to its well-characterised genetic background, capacity for high-density fermentation, and effective protein secretion. With the growing global demand for recombinant proteins across various sectors, there is an increasing need for more efficient and sustainable protein production methods. This review explores the application of continuous bioprocessing for recombinant protein production using B. subtilis, critically evaluating current technologies and discussing their potential for integration into streamlined, integrated biomanufacturing framework. We primarily focus on transgenic B. subtilis, however the solutions for continuous fermentation and protein isolation/purification are the same for both endogenous and heterologous (i.e., recombinant) proteins.

• Language: English
• Keywords: continuous bioprocessing, Bacillus subtilis, upstream processing, downstream processing, recombinant protein production
• Work type: Article
• Typology: 1.02 - Review Article
• Organization: BF - Biotechnical Faculty; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: Str. 126-133
• Numbering: Vol. 68, no. 4
• PID: 20.500.12556/RUL-179383
• UDC: 577.112
• ISSN on article: 1854-3073
• DOI: 10.14720/abs.68.4.22623
• COBISS.SI-ID: 264924931
• Publication date in RUL: 12.02.2026

Record is a part of a journal

• Title: Acta biologica slovenica
• Publisher: Društvo biologov Slovenije, Društvo biologov Slovenije, Založba Univerze v Ljubljani, Društvo biologov Slovenije
• ISSN: 1854-3073
• COBISS.SI-ID: 221921024

Secondary language

• Language: Slovenian
• Title: Kontinuirno bioprocesništvo za proizvodnjo rekombinantnih proteinov v Bacillus subtilis : priložnosti in izzivi

Abstract

Po Gramu pozitivno bakterijo Bacillus subtilis že dolgo uporabljamo v industrijski proizvodnji proteinov. K temu prispevajo njena dobra raziskana genetska zasnova, možnost doseganja visoke biomase med fermentacijo in učinkovito izločanje proteinov. Zaradi naraščajočega svetovnega povpraševanja po rekombinantnih proteinih v različnih sektorjih, se povečuje tudi potreba po učinkovitejših in trajnostnih metodah proizvodnje proteinov. V članku predstavljamo potencial kontinuirnega bioprocesništva pri proizvodnji rekombinantnih proteinov z uporabo B. subtilis. Ponujamo pregled obstoječih tehnologij in njihovega potenciala za vključitev v integrirani koncept učinkovitejše bioproizvodnje rekombinantnih proteinov. Čeprav se prispevek primarno posveča transgenim bakterijam B. subtilis, so rešitve kontinuirne fermentacije in izolacije/čiščenja proteinov enake za endogene in heterologne (tj. rekombinantne) proteine.

• Keywords: kontinuirno bioprocesiranje, Bacillus subtilis, pripravljalni procesi, zaključni postopki, proizvodnja rekombinantnih proteinov